The murine glucagon-like peptide-1 receptor is essential for control of bone resorption

Gastrointestinal hormones including gastric inhibitory polypeptide (GIP), glucagon-like peptide (GLP)-1, and GLP-2 are secreted immediately after meal ingestion, and GIP and GLP-2 have been shown to regulate bone turnover. We hy-pothesize that endogenous GLP-1 may also be important for control of skeletal homeostasis. We investigated the role of GLP-1 in the regulation of bone metabolism using GLP-1 re-ceptor knockout (Glp-1r/) mice. A combination of bone den-sity and histomorphometry, osteoclast activation studies, bio-chemical analysis of calcium and PTH, and RNA analysis was used to characterize bone and mineral homeostasis in Glp-1r/ and Glp-1r/ littermate controls. Glp-1r/ mice have cortical osteopenia and bone fragility by bone densitometry aswell as increasedosteoclastic numbers andbone resorption activity by bone histomorphometry. Although GLP-1 had n